Prognostic value of FLT3 mutations among different cytogenetic subgroups in acute myeloid leukemia

Fabio P.S. Santos, Dan Jones, Wei Qiao, Jorge E. Cortes, Farhad Ravandi, Elihu E. Estey, Dushyant Verma, Hagop Kantarjian, Gautam Borthakur

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The impact of FMS-like tyrosine kinase 3 (FLT3) mutations and mutation burden among cytogenetic subgroups of patients with acute myeloid leukemia (AML) other than normal karyotype (NK) AML is unclear. METHODS: Patients with newly diagnosed AML were divided among 3 cytogenetic subgroups: core binding factor (CBF) AML, NK-AML, and poor-risk AML. RESULTS: In total, 481 patients were included: 13% had, CBF-AML, 57% had NK-AML, and 30% had poor risk AML, and the frequency of any FLT3 mutations was 20%, 32%, and 7.6% in the respective cytogenetic subgroups. FLT3 mutation did not have an impact on event-free survival (EFS) in patients with CBF-AML (P =.84) and poor-risk AML (P =.37). In patients with NK-AML, EFS was worse in the FLT3-internal tandem duplication (ITD) group (20 weeks vs 41 weeks; P <.00,001) but not in the FLT3-tyrosine kinase domain (TKD) point mutation group (61 weeks vs 41 weeks; P =.15). Worse EFS and overall survival (OS) were observed among patients with NK-AML and higher FLT3-ITD burden but not among patients with FLT3-TKD mutation. In multivariate analysis, FLT3-ITD mutation was prognostic of EFS in patients with NK-AML (hazard ratio, 3.1; P =.03). CONCLUSIONS: FLT3 mutations did not have a prognostic impact in patients with AML who had good-risk and poor-risk karyotypes. In patients with NK-AML, FLT3-ITD mutations led to worse survival, which was even worse among patients who had high mutation burden.

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Acute Myeloid Leukemia
Cytogenetics
Protein-Tyrosine Kinases
Mutation
Karyotype
Core Binding Factors
Disease-Free Survival
Survival
Point Mutation
Multivariate Analysis

Keywords

  • acute myeloid leukemia
  • cytogenetics
  • FMS-like tyrosine kinase 3
  • prognostic factors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Santos, F. P. S., Jones, D., Qiao, W., Cortes, J. E., Ravandi, F., Estey, E. E., ... Borthakur, G. (2011). Prognostic value of FLT3 mutations among different cytogenetic subgroups in acute myeloid leukemia. Cancer, 117(10), 2145-2155. https://doi.org/10.1002/cncr.25670

Prognostic value of FLT3 mutations among different cytogenetic subgroups in acute myeloid leukemia. / Santos, Fabio P.S.; Jones, Dan; Qiao, Wei; Cortes, Jorge E.; Ravandi, Farhad; Estey, Elihu E.; Verma, Dushyant; Kantarjian, Hagop; Borthakur, Gautam.

In: Cancer, Vol. 117, No. 10, 15.05.2011, p. 2145-2155.

Research output: Contribution to journalArticle

Santos, FPS, Jones, D, Qiao, W, Cortes, JE, Ravandi, F, Estey, EE, Verma, D, Kantarjian, H & Borthakur, G 2011, 'Prognostic value of FLT3 mutations among different cytogenetic subgroups in acute myeloid leukemia', Cancer, vol. 117, no. 10, pp. 2145-2155. https://doi.org/10.1002/cncr.25670
Santos, Fabio P.S. ; Jones, Dan ; Qiao, Wei ; Cortes, Jorge E. ; Ravandi, Farhad ; Estey, Elihu E. ; Verma, Dushyant ; Kantarjian, Hagop ; Borthakur, Gautam. / Prognostic value of FLT3 mutations among different cytogenetic subgroups in acute myeloid leukemia. In: Cancer. 2011 ; Vol. 117, No. 10. pp. 2145-2155.
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abstract = "BACKGROUND: The impact of FMS-like tyrosine kinase 3 (FLT3) mutations and mutation burden among cytogenetic subgroups of patients with acute myeloid leukemia (AML) other than normal karyotype (NK) AML is unclear. METHODS: Patients with newly diagnosed AML were divided among 3 cytogenetic subgroups: core binding factor (CBF) AML, NK-AML, and poor-risk AML. RESULTS: In total, 481 patients were included: 13{\%} had, CBF-AML, 57{\%} had NK-AML, and 30{\%} had poor risk AML, and the frequency of any FLT3 mutations was 20{\%}, 32{\%}, and 7.6{\%} in the respective cytogenetic subgroups. FLT3 mutation did not have an impact on event-free survival (EFS) in patients with CBF-AML (P =.84) and poor-risk AML (P =.37). In patients with NK-AML, EFS was worse in the FLT3-internal tandem duplication (ITD) group (20 weeks vs 41 weeks; P <.00,001) but not in the FLT3-tyrosine kinase domain (TKD) point mutation group (61 weeks vs 41 weeks; P =.15). Worse EFS and overall survival (OS) were observed among patients with NK-AML and higher FLT3-ITD burden but not among patients with FLT3-TKD mutation. In multivariate analysis, FLT3-ITD mutation was prognostic of EFS in patients with NK-AML (hazard ratio, 3.1; P =.03). CONCLUSIONS: FLT3 mutations did not have a prognostic impact in patients with AML who had good-risk and poor-risk karyotypes. In patients with NK-AML, FLT3-ITD mutations led to worse survival, which was even worse among patients who had high mutation burden.",
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AU - Santos, Fabio P.S.

AU - Jones, Dan

AU - Qiao, Wei

AU - Cortes, Jorge E.

AU - Ravandi, Farhad

AU - Estey, Elihu E.

AU - Verma, Dushyant

AU - Kantarjian, Hagop

AU - Borthakur, Gautam

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N2 - BACKGROUND: The impact of FMS-like tyrosine kinase 3 (FLT3) mutations and mutation burden among cytogenetic subgroups of patients with acute myeloid leukemia (AML) other than normal karyotype (NK) AML is unclear. METHODS: Patients with newly diagnosed AML were divided among 3 cytogenetic subgroups: core binding factor (CBF) AML, NK-AML, and poor-risk AML. RESULTS: In total, 481 patients were included: 13% had, CBF-AML, 57% had NK-AML, and 30% had poor risk AML, and the frequency of any FLT3 mutations was 20%, 32%, and 7.6% in the respective cytogenetic subgroups. FLT3 mutation did not have an impact on event-free survival (EFS) in patients with CBF-AML (P =.84) and poor-risk AML (P =.37). In patients with NK-AML, EFS was worse in the FLT3-internal tandem duplication (ITD) group (20 weeks vs 41 weeks; P <.00,001) but not in the FLT3-tyrosine kinase domain (TKD) point mutation group (61 weeks vs 41 weeks; P =.15). Worse EFS and overall survival (OS) were observed among patients with NK-AML and higher FLT3-ITD burden but not among patients with FLT3-TKD mutation. In multivariate analysis, FLT3-ITD mutation was prognostic of EFS in patients with NK-AML (hazard ratio, 3.1; P =.03). CONCLUSIONS: FLT3 mutations did not have a prognostic impact in patients with AML who had good-risk and poor-risk karyotypes. In patients with NK-AML, FLT3-ITD mutations led to worse survival, which was even worse among patients who had high mutation burden.

AB - BACKGROUND: The impact of FMS-like tyrosine kinase 3 (FLT3) mutations and mutation burden among cytogenetic subgroups of patients with acute myeloid leukemia (AML) other than normal karyotype (NK) AML is unclear. METHODS: Patients with newly diagnosed AML were divided among 3 cytogenetic subgroups: core binding factor (CBF) AML, NK-AML, and poor-risk AML. RESULTS: In total, 481 patients were included: 13% had, CBF-AML, 57% had NK-AML, and 30% had poor risk AML, and the frequency of any FLT3 mutations was 20%, 32%, and 7.6% in the respective cytogenetic subgroups. FLT3 mutation did not have an impact on event-free survival (EFS) in patients with CBF-AML (P =.84) and poor-risk AML (P =.37). In patients with NK-AML, EFS was worse in the FLT3-internal tandem duplication (ITD) group (20 weeks vs 41 weeks; P <.00,001) but not in the FLT3-tyrosine kinase domain (TKD) point mutation group (61 weeks vs 41 weeks; P =.15). Worse EFS and overall survival (OS) were observed among patients with NK-AML and higher FLT3-ITD burden but not among patients with FLT3-TKD mutation. In multivariate analysis, FLT3-ITD mutation was prognostic of EFS in patients with NK-AML (hazard ratio, 3.1; P =.03). CONCLUSIONS: FLT3 mutations did not have a prognostic impact in patients with AML who had good-risk and poor-risk karyotypes. In patients with NK-AML, FLT3-ITD mutations led to worse survival, which was even worse among patients who had high mutation burden.

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